Characterization and functional analysis of Oct4 isoforms in human mesenchymal stem cells.

摘要

Mesenchymal stem cells (MSCs) are well-known for their capacity to self-renew and differentiate into one or more specialized cell types. The mechanisms governing multipotency in MSCs are not well understood, but have been partially attributed to the expression of Oct4---a transcription factor that regulates the maintenance of a pluripotent state in embryonic stem cells (ESCs). Oct4 expression has also been reported in several cell populations and has been employed to provide evidence of stemness. Three isoforms of Oct4 have been reported: Oct4A, Oct4B, and Oct4B1. Oct4A is absolutely essential for maintaining pluripotency in ESCs, while the functions of Oct4B and Oct4B1 remain unclear. However, it has been suggested that Oct4B may respond to cell stress and Oct4B1may act as an antiapoptotic factor in cancer cells. In the literature, the lack of distinction of Oct4 isoforms that are expressed has resulted in uncertainty and debate surrounding Oct4. In this study, the expression pattern of each Oct4 isoform in both human adipose and bone marrow derived stem cells is reported. At the mRNA level, all Oct4 variant mRNAs were transcribed; however, only Oct4B or Oct4B1 proteins were detected.;Mesenchymal stem cells demonstrate plasticity and express Oct4 isoforms with similar homology to Oct4A. We demonstrate that Oct4 variants are important to the multipotency of mesenchymal stem cells by targeting Oct4 variants by short-hairpin RNA interference. Oct4 suppressed cells displayed impaired ability to differentiate into osteogenic and adipogenic lineages. This study reveals the significance of Oct4 variant expression regarding plasticity in somatic stem cells and provides conjecture of a conserved regulatory mechanism between Oct4B and/or Oct4B1 with Oct4A.